Characterization of Macroglia Response during Tissue Repair in a Laser-Induced Model of Retinal Degeneration

Reactive gliosis is a hallmark of chronic degenerative diseases of the retina. As gliosis involves macroglia, we investigated their gliotic response to determine the role of S100 beta and intermediate filaments (IFs) GFAP, vimentin, and nestin during tissue repair in a laser-induced model of retinal degeneration. We validated the results with human retinal donor samples. Experiments were performed in zebrafish and mice using an argon laser (532 nm) to induce focal lesions in the outer retina. At different time points following injury induction, the kinetics of retinal degeneration and regeneration were assessed using hematoxylin and eosin staining (H&E). Immunofluorescence was performed to evaluate Muller cell (GS) and astrocyte (GFAP) injury response and to distinguish between both cell types. Additionally, staining was performed in human retinal sections containing drusen. Focal laser treatment elevated the expression of gliotic markers in the area of the damage, which was associated with increased expression of S100 beta, GFAP, vimentin, and nestin in mice and humans. In zebrafish, we detected S100 beta at the first time point, but not GFAP or nestin. Doublepositive cells with the selected glia markers were detected in all models. However, in zebrafish, no double-positive GFAP/GS cells were found on days 10 and 17, nor were S100 beta/GS double-positive cells found on day 12. Macroglia cells showed a different pattern in the expression of IFs in degenerative and regenerative models. In particular, S100 beta may prove to be a target for suppressing chronic gliosis in retinal degeneration.